Metabotropic glutamate receptor 4

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Glutamate receptor, metabotropic 4
Identifiers
SymbolsGRM4; GPRC1D; MGLUR4; mGlu4
External IDsOMIM604100 MGI1351341 HomoloGene20230 IUPHAR: mGlu4 GeneCards: GRM4 Gene
RNA expression pattern
250px
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez2914268934
EnsemblENSG00000124493ENSMUSG00000063239
UniProtQ14833Q68EF4
RefSeq (mRNA)NM_000841NM_001013385
RefSeq (protein)NP_000832NP_001013403
Location (UCSC)Chr 6:
34.1 - 34.23 Mb
Chr 17:
27.15 - 27.23 Mb
PubMed search[1][2]

Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.[1][2][3]

Together with GRM6, GRM7 and GRM8 it belongs to group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.[3] Activation of GRM4 has potential therapeutic benefits in the treatment of parkinson's disease. "Taste-GRM4" is involved in the perception of umami.

Ligands

Orthosteric

  • LSP1-2111, LSP1-3081: agonists

Allosteric

  • heterobiaryl amides 9b and 9c: positive allosteric modulators (PAM)[4]
  • VU-001171: PAM with EC50 = 650 nM, 141% Glu Max, 36-fold shift[5]
  • VU-0155041: subtype-selectve PAM, intrinsic allosteric agonist activity, robust in-vivo activity[6]
  • PHCCC: PAM of mGluR4, negative allosteric modulator of mGluR1,[7] direct agonist at mGluR6[8]

References

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External links

Further reading

  • Flor PJ, Lukic S, Rüegg D; et al. (1995). "Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4". Neuropharmacology. 34 (2): 149–55. doi:10.1016/0028-3908(94)00149-M. PMID 7617140. 
  • Scherer SW, Duvoisin RM, Kuhn R; et al. (1997). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics. 31 (2): 230–3. doi:10.1006/geno.1996.0036. PMID 8824806. 
  • Gomeza J, Mary S, Brabet I; et al. (1996). "Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists". Mol. Pharmacol. 50 (4): 923–30. PMID 8863838. 
  • Fu M, Wang C, Reutens AT; et al. (2000). "p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation". J. Biol. Chem. 275 (27): 20853–60. doi:10.1074/jbc.M000660200. PMID 10779504. 
  • Barbon A, Ferraboli S, Barlati S (2000). "Assignment of the human metabotropic glutamate receptor gene GRM4 to chromosome 6 band p21.3 by radiation hybrid mapping". Cytogenet. Cell Genet. 88 (3-4): 210. doi:10.1159/000015551. PMID 10828590. 
  • Ohtsuki T, Toru M, Arinami T (2002). "Mutation screening of the metabotropic glutamate receptor mGluR4 (GRM4) gene in patients with schizophrenia". Psychiatr. Genet. 11 (2): 79–83. doi:10.1097/00041444-200106000-00004. PMID 11525421. 
  • Erdemir T, Bilican B, Oncel D; et al. (2002). "DNA damage-dependent interaction of the nuclear matrix protein C1D with Translin-associated factor X (TRAX)". J. Cell. Sci. 115 (Pt 1): 207–16. PMID 11801738. 
  • Collard CD, Park KA, Montalto MC; et al. (2002). "Neutrophil-derived glutamate regulates vascular endothelial barrier function". J. Biol. Chem. 277 (17): 14801–11. doi:10.1074/jbc.M110557200. PMID 11847215. 
  • Enz R (2002). "The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7". FEBS Lett. 514 (2-3): 184–8. doi:10.1016/S0014-5793(02)02361-X. PMID 11943148. 
  • Gaughan L, Logan IR, Cook S; et al. (2002). "Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor". J. Biol. Chem. 277 (29): 25904–13. doi:10.1074/jbc.M203423200. PMID 11994312. 
  • Mungall AJ, Palmer SA, Sims SK; et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404. 
  • Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
  • Iacovelli L, Capobianco L, Iula M; et al. (2004). "Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2)". Mol. Pharmacol. 65 (5): 1103–10. doi:10.1124/mol.65.5.1103. PMID 15102938. 
  • Hermit MB, Greenwood JR, Bräuner-Osborne H (2004). "Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4: ligand selectivity results from a synergy of several amino acid residues". J. Biol. Chem. 279 (33): 34811–7. doi:10.1074/jbc.M404109200. PMID 15184361. 
  • Yoo BC, Jeon E, Hong SH; et al. (2005). "Metabotropic glutamate receptor 4-mediated 5-Fluorouracil resistance in a human colon cancer cell line". Clin. Cancer Res. 10 (12 Pt 1): 4176–84. doi:10.1158/1078-0432.CCR-1114-03. PMID 15217955. 
  • Chang HJ, Yoo BC, Lim SB; et al. (2005). "Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance". Clin. Cancer Res. 11 (9): 3288–95. doi:10.1158/1078-0432.CCR-04-1912. PMID 15867225. 
  • Mathiesen JM, Ramirez MT (2006). "The metabotropic glutamate receptor 4 is internalized and desensitized upon protein kinase C activation". Br. J. Pharmacol. 148 (3): 279–90. doi:10.1038/sj.bjp.0706733. PMC 1751557Freely accessible. PMID 16582932. 
  • Iacovelli L, Arcella A, Battaglia G; et al. (2006). "Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the growth of medulloblastomas". J. Neurosci. 26 (32): 8388–97. doi:10.1523/JNEUROSCI.2285-06.2006. PMID 16899734. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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  3. 3.0 3.1 "Entrez Gene: GRM4 glutamate receptor, metabotropic 4". 
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  5. Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW (2009). "Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead". Bioorg. Med. Chem. Lett. 19 (3): 962–6. doi:10.1016/j.bmcl.2008.11.104. PMID 19097893. 
  6. Niswender CM, Johnson KA, Weaver CD; et al. (2008). "Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4". Mol. Pharmacol. 74 (5): 1345. doi:10.1124/mol.108.049551. PMC 2574552Freely accessible. PMID 18664603. 
  7. Watkins JC, Jane DE (2006). "The glutamate story". British journal of pharmacology. 147 Suppl 1: S100–8. doi:10.1038/sj.bjp.0706444. PMC 1760733Freely accessible. PMID 16402093. 
  8. Beqollari D, Kammermeier PJ (2008). "The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors". European journal of pharmacology. 589 (1-3): 49–52. doi:10.1016/j.ejphar.2008.06.054. PMID 18593581.